Physical pharmacy processes 2

Physical Pharmacy Processes

1. Calcination SaMIA GHANI

2. DEFINITION the heating of solids to a high temperature for the purpose of removing volatile substances, oxidizing a portion of mass, or rendering them friable. Calcination, therefore, is sometimes considered a process of purification . Calcinations is the process of subjecting a substance to the action of heat, but without fusion, for the purpose of causing some change in its physical or chemical constitution . Calcination  refers to heating a solid to high temperatures in absence of air or oxygen, generally for the purpose of removing impurities or  volatile  substances. [1]  However, calcination is also used to mean a  thermal treatment  process in the absence or limited supply of air or oxygen applied to  ores  and other solid materials to bring about a  thermal decomposition .  The root of the word calcination refers to its most prominent use, which is to remove carbon from  limestone  through  combustion  to yield  calcium oxide (quicklime) . This calcination reaction is CaCO 3 (s) → CaO (s) + CO 2 (g). Calcium oxide is a crucial ingredient in modern  cement , and is also used as a chemical  flux  in  smelting . Industrial calcination generally emits  carbon dioxide  (CO 2), making it a major contributor to  climate change .

3. OBJECTIVE OF CALCINATION to drive off water, present as absorbed moisture, as "water of crystallization," or as "water of constitution"; to drive off carbon dioxide, sulphl11' dioxide, or other volatile constituent; to oxidize a part or the whole of the substance. 'there are a few other purposes for which calcination is employed in special cases, and these will be mentioned in their propel' places. The process is often called "roasting," "firing," or "burning," by the workmen. It is carried on in furnaces, retorts, or kilns, and very often the material is raked over or stirred, during the process, to secure uniformity in the product .

4. examples Some examples of calcination include; Calcination of limestone involving decomposition of carbonate ores and removal of carbon dioxide . Calcination of Gypsum Calcination of bauxite and gypsum involving the removal of water of crystallization in the form of water vapour . Decomposition of volatile components from raw petroleum coke. Obtaining rutile from anatase or devitrification of glass materials. Synthesis of zeolites where ammonium ions are removed. Anhydrous alumina is left behind when bauxite is calcined and water is removed. Al 2 O3.2H 2 O → Al 2 O3 + 2H 2 O Anhydrous iron is formed during iron calcination. 2Fe 2 O 3 .3H 2 O → 2Fe 2 O 3  + 3H 2 O

5. Muffle furnaces   are so constructed that neither the fuel nor the fire gases come in direct contact with the material to be calcined . A retort of iron, brickwork, or fire-clay, is placed over the fire grate (G). Flues (F. F) are built around the retort, and through these the hot gases from the fire pass on their way to the chimney (E ).

6. Principle of calcination Heating a substance below its fusing points or melting points at a high temperature which causes oxidation or reduction, loss of moisture and decomposition of carbonates and other substances. Calcination is usually carried out in furnaces, retorts, or kilns and often materials are racked over or stirred to make sure the product is uniform. One of the common arrangement that is used for calcination is the reverberatory furnace. The typical construction and process are explained below There are different forms of construction for reverberatory furnaces, but in all cases, the flames and hot gases from the fire come in direct contact with the material to be calcined , however, the fuel is separated from it. In the above figure, the fire burns on the grate at G. Now the flames passing over the bridge at E are deflected downward by the low sloping roof of the furnace and pass directly over the surface of the charge or the material under calcination which is laid on the platform B. The fumes and hot gases then escape through the throat F into the chimney. The charge is spread out evenly on the bed as a thin layer .

7. Reverberatory furnaces  They are built in many forms, but in all cases the flames and hot gases from the fire come in direct contact with the material to be calcined , but the fuel is separated from it. The fire burns on the grate at (G), and the flames, passing over the bridge at (E), are deflected down ward by the low sloping roof of the furnace, and pass directly over the surface of the charge in the bed of the furnace at (B), finally escaping through the throat (F) into the chimney. The charge is spread out in a thin layer on the bed (B), and may be either oxidized or reduced according to the method of firing and the amount of air admitted. The revolving furnace (Figs. 3 and 39) is a very important modification of the reverberatory furnace. This consists of a horizontal or slightly inclined cylinder (B) of iron or steel plates, lined with fire-brick or other suitable fire-resisting material, and open at each end. The flames from a grate (A) at one end pass through it on their way

8. The cylinder is revolved about its.  longitudinal axis  by means of a gear. It is turned until a manhole in the side is brought directly under a hole in the floor above, the bolted cover is removed, and the charge dumped in. The revolution of the cylinder stirs the charge thoroughly, and brings it into intimate contact with the flame. To discharge the contents, the cylinder is stopped when the manhole is on the under side, the cover is removed, and the material drops out upon the floor or into a car placed for it. To facilitate discharging, the lining usually slopes from all sides towards the manhole. The speed varies from about two revolutions a minute to one revolution in five or ten minutes. These furnaces are now extensively used, their advantages being the intimate mixing and even heating of the charge, and the large quantities, amounting often to several tons, which can be worked at one time.

9. Difference Between Calcination and Roasting Calcination Roasting Calcination is the process in which the ore of the metal is heated to high temperature in the absence or limited supply of air or oxygen. Roasting is the process in which the ore is heated to high temperatures in the presence of excess supply of air or oxygen. Calcination consists of thermal decomposition of calcium ores. Roasting is mostly done for sulphide ores. Carbon dioxide is given out as a by-product During roasting, large quantities of toxic, metallic and acid impurities are driven out. During calcination, moisture is removed from the ore. Roasting is not used for the removal of moisture.

10. applications Calcination of Gypsum Gypsum or Calcium sulfate dihydrate (CaSo 4 .2H 2 O) is a mineral of calcium that is mined in various parts of the world. It is also formed as a by-product of flue gas desulphurization in some coal-fired electric power plants. There are different kinds of Gypsum and are listed below. Alabaster – pure white, fine-grained and translucent gypsum. Satin spar, gypsum with fibrous needle-like crystals with a silky lustre . Selenite, colourless and transparent crystals. Gypsum is used in many fields. Some major domains are listed below. Building construction Soil conditioning Food additives Pharmaceuticals Medical devices

11. Calcination reactions usually take place at or above the thermal decomposition temperature (for decomposition and volatilization reactions) or the transition temperature (for phase transitions). This temperature is usually defined as the temperature at which the standard  Gibbs free energy  for a particular calcination reaction is equal to zero . Limestone calcination [ edit ] In limestone calcination, a decomposition process that occurs at 900 to 1050ºC, the chemical reaction is CaCO 3 (s) → CaO (s) + CO 2 (g) Today , this reaction largely occurs in a cement kiln The standard Gibbs free energy of reaction is approximated as  ΔG° r  ≈ 177,100 − 158  T  (J/ mol ).The standard free energy of reaction is 0 in this case when the temperature,  T , is equal to 1121 K, or 848 °C . The furnaces used for calcining substances vary much in their construction, but there are three general classes: muffle, reverberatory , and shaft furnaces or kilns . Limestone  has numerous  uses : as a building material, an essential component of concrete (Portland cement), as aggregate for the base of roads, as white pigment or filler in products such as toothpaste or paints, as a chemical feedstock for the production of lime, as a soil conditioner, and as a popular decorative 

12. Adsorption

13. A d s o r p t i o n v s . A bs o rp t i o n Adsorption is accumulation of molecules on a surface (a surface layer of molecules) in contact with an air o r w a ter pha s e Absorption is dissolution of molecules within a phase, e.g., within an organic phase in contact with an air or w a t er pha s e ad s o r b a t e : ma teri a l bei ng a d s o rbed ad s o r b e n t : ma teri a l d o i ng t h e a d s o rb i n g . ( ex a mp l e s a r e a c t i v a ted c a r b o n o r i o n exch a n g e res i n) .

14. A d sor p t i o n Absorption (“partitioning”) PHASE I PHASE 2 PHASE I ‘PHASE’ 2 P gas  K H c aq Henry’s Law

15. Physisorption or physical adsorption is a type of adsorption in which the adsorbate adheres to the surface only through Van der Waals (weak intermolecular) interactions, which are also responsible for the non-ideal behaviour of real gases. Chemisorption in this kind of adsorption, the gas molecules or atoms are held to the solid by chemical bonds. For example hydrogen is chemisorbed on nickel.

16. S.No Physical adsorption Chemical adsorption 1. Caused by intermolecular forces Caused by chemical bond formation 2 . Heat of adsorption is small Heat of adsorption is large 3 . Reversible Irr e v e r s i b l e 4 . Forms multimolecular layer Forms unimolecular layer 5 . Decreases with increasing temperature Increases with increasing of temperature 6 . Depends on nature of gas Much more specific than physical adsorption 7 . Increase of pressure increases adsorption, decrease of pressure causes of desorption Change of pressure has no such effects

17. Some common examples of adsorption are silica gel packets to adsorb moisture from packaged electronic or optical equipment, and carbon "filter" to deodorize drinking water. In pharmacy, activated charcoal is considered to be the most effective single agent available as an emergency decontaminant in the gastrointestinal tract. It is used after a person swallows or absorbs almost any toxic drug or chemical. Adsorption is usually described through isotherms, that is, functions which connect the amount of adsorbate on the adsorbent, with its pressure (if gas) or concentration (if liquid). One can find in literature several models describing process of adsorption, namely Freundlich isotherm, Langmuir isotherm, BET isotherm, etc.

18. Applications of adsorption Production of high vacuum If a partially evacuated vessel is connected to a container of activated charcoal cooled with liquid air, the charcoal adsorbs all the gas molecules in the vessel. This results in a very vacuum. Gas mask Gas masks are devices contain an adsorbent (activated charcoal) or a series of adsorbents; these adsorbents remove poisonous gases by adsorption and purify the air for breathing. Heterogeneous catalysis In a heterogeneous catalysis, the molecules of the reactant are adsorbed at the catalyst surface, where they form an “adsorption complex”. This decomposes to form the product molecules which then take off from the surface.

19. Removal of coloring matter from solutions Animal charcoal removes colours of solution by adsorbing coloured impurities thus in the manufacture of cane-sugar, the coloured solution is clarified by treating with animal charcoal or activated charcoal. Chromatographic analysis Mixtures of small quantities of organic substances can be separated with the help of chromatography which involves the principles of selective adsorption.

20. decantation

21. Decantation  is a process for the  separation of mixtures  of  immiscible  liquids or of a liquid and a solid mixture such as a  suspension The layer closer to the top of the container—the less  dense  of the two liquids, or the liquid from which the  precipitate  or  sediment  has settled out—is poured off, leaving the other component or the more dense liquid of the mixture behind. An incomplete separation is witnessed during the separation of two immiscible liquids. To put it in a simple way decantation is separating an immiscible solution by transferring the top layer of the solution to another container.

22. processes Immiscible liquid separation [ edit ] Decantation can be used to separate immiscible liquids that have different densities. For example, when a mixture of water and oil is present in a beaker, a distinct layer between the two consistency is formed, with the oil layer floating on top of the water layer. This separation can be done by pouring oil out of the container, leaving water behind. [2]  Generally, this technique gives an incomplete separation as it is difficult to pour off all of the top layer without pouring out some parts of the bottom layer. A  separatory funnel  is an alternative apparatus for separating liquid layers. [2]  It has a valve at the bottom to allow draining off the bottom layer. It can give better separation between the two liquids.

23. Liquid-solid separation Decantation can also separate solid and liquid mixtures by allowing  gravity  to pull the solid fragments to settle at the bottom of the container. [3]  In laboratory situations, decantation of mixtures containing solids and liquids occur in  test tubes . To enhance productivity, test tubes should be placed at a 45° angle to allow sediments to settle at the bottom of the apparatus. [4] A  centrifuge  may also be used in decantation as the natural process of settling down is time-consuming and tedious. [1]  A centrifuge forces the  precipitate  to the bottom of the container; if the force is high enough, solids can aggregate to form pellets, making it easier to separate the mixtures. [3]  Then the liquid can be more easily poured away, as the precipitate will tend to remain in its compressed form.  A  decanter centrifuge  may be used for continuous solid-liquid separation.

24. Decantation is frequently used to purify a liquid by separating it from a suspension of  insoluble  particles (e.g. in red  wine , where the wine is decanted from the  potassium bitartrate  crystals to avoid unsavory taste ).  This makes the wine more tonic and astringent. Cream accelerates to the top of milk, allowing the separation of milk and cream. This is used in the cheese industry .  Fat is determined in butter by decantation . To obtain a sample of clear water from muddy water, muddy water is poured into another container, which separates the water from the mud . In the sugar industry, the processing of sugar beets into granular sugar and many liquid - solid separations are encountered e.g. separation of syrups from crystals .

25. Decantation is also present in  nanotechnology . In the synthesis of high quality silver nanowire ( AgNW ) solutions and fabrication process of high performance electrodes, decantation is also being applied which greatly simplifies the purification process . After using a  desiccant  to absorb water from an organic liquid, the organic liquid can often be decanted away from the desiccant . The process of deriving vinegar also requires decantation to remove fats and biomolecular antioxidants from the raw substance . Plasma can be separated from blood through decantation by using a centrifuge . Mercury is disposed of in water bodies during mining, turning the water unfit and toxic. The mercury can be removed through decantation .

26. centrifugation

27. Centrifugation is a process use d to m a ter i a l s separate suspend e d or concentrate i n a liq u i d me d iu m. The theoretical basis of this technique is the effect of gravity on particles (including macromolecules) in suspension. Two particles of different masses will settle in a tube at different rates in response to gravity.

28.  Cent r ifu g a tio n i s a pr o ce s s w hic h inv o l v e s the use of the centrifugal force for the sedimentation of heterogeneous mixtures with a centrifuge, used in industry and in laboratory settings. This process is used to separate two immiscible liquids. More-dense components of the mixture migrate away from the axis of the centrifuge, while less- dense components of the mixture migrate towards the axis .

29. A centrifuge is a device for separating particles from a solution according to their size, shape, density, viscosity of the medium and rotor speed. In a solution, particles whose density is higher than that of the solvent sink (sediment), and particles that are lighter than it float to the top. The greater the difference in density, the faster they move. If there is no difference in density (isopyknic conditions), the particles stay steady.

30.  To take advantage of even tiny differences in density to separate various particles in a solution, gravity can be replaced with the much more powerful “ centrifugal force” provided by a centrifuge.

31.  It consist of two components, an electric motor to spin the sample and a rotor to hold tubes. LOW SPEED CENTRIFUGE HIGH SPEED CENTRIFUGE ULTRA CENTRIFUGE

32. Most laboratories have a standard low-speed centrifuge used for routine sedimentation of heavy particles. The low speed centrifuge has a maximum speed of 4000-5000rpm. usu ally operate a t r o om n o mea n s o f tem p eratu r e  These instruments temperatures with control. Two types of rotors are used in it, fixed angle and swinging bucket. It is used for sedimentation of red blood cells until the particles are tightly packed into a pellet and supernatant is separated by decantation.

33.  H i gh sp e ed c e ntr i fug e s ar e use d in more sophisticated biochemical applications, higher speeds and temperature control of the rotor chamber are essential. The operator of this instrument can carefully control speed and temperature which is required for sensitive biological samples. Three types of rotors are available for high speed centrifugation-fixed angle, swinging bucket, vertical rotors

34. It is the most sophisticated instrument Intense heat is generated due to high speed thus the spinning chambers must be refrigerated and kept at high vacuum. It is used for both preparative work and analytical work.

35. Types of Centrifugati o n Techniques Density gradient centrifu g ati o n Differential cen t rifu g ati o n Ultra cen t rifu g ati o n

36. It allow separation of many or all components in a mixture and allows for measurement to be made There are two forms of Density gradient centrifugation : Rate zonal centrifugation Isopycnic or sedimentation equilibrium centrifugation

37.  Rate zonal centrifugation The particles will begin sedimenting in separate zones according to their size shape and density.

38. Isopycnic or sedimentation equilibrium centrifugation In Isopycnic centrifugation separation of particles occurs into zones on the basis of their density differences, independent of ti m e.

39.  Differential c e ntr i fugati o n is a comm o n procedure in microbiology and cytology used to separate certain organelles from whole cells for further analysis of specific parts of cells. first homog e n iz e d to b r e a k the  I n th e p ro c ess , a t i s s u e sa m p le is c e ll membranes and mix up the cell contents.  The homogenate is then subjected to repeated centrifugations, each time removing the pellet and increasing the centrifugal force.

40. Svedberg coined the term “ultracentrifuge". He was colloid chemist. He used the ultracentrifuge to determine the MW and subunit structure of hemoglobin , studies which changed the ideas concerning the structure of proteins. The first commercial ultracentrifuge was produced in 1940 by SPINCO.

41. An important tool in biochemical research is the centrifuge, which through rapid spinning imposes high centrifugal forces on suspended particles, or even molecules in solution, and causes separations of such matter on the basis ULTRACENTRIFUGATION of differences in weight. Example: Red cells may be separated from plasma of blood, nuclei from mitochondria in cell homogenates, and one protein from another in complex mixtures

42. Applications of Centrifugation in Pharmaceutical Industries Production of bulk drugs After crystallization the drugs are separated from the mother liquor by centrifugation. For example traces of mother liquor is separated from aspirin crystals by centrifugation method. 2. Production of biological products Most of the biological products are either proteinaceous or macromolecules. During manufacturing they remain in colloidal dispersion in water. By normal methods of filtration it is difficult to separate the colloid particles. In those cases centrifugal methods are used. Insulin is purified from other precipitates of protein materials by centrifugation. Blood cells are separated from plasma by centrifugal method. Bacterial enzymes are separate from bacterial culture medium by sedimenting the bacterial cells by centrifugation. Dirt and water are separated from olive oil and fish-liver oils .

43. 3. Evaluation of suspensions and emulsions One of the problems of suspensions is sedimentation and one of the problems of emulsions is creaming. Immediately after the preparation of a suspension or emulsion this problems may not appear quickly. To enhance the rate of sedimentation and creaming the suspension or emulsion is introduced in a centrifuge and rotate at an rpm of 200 to 3000. If still the problems do not appear then the suspension or emulsion can be taken as stable formulation. 4. Determination of molecular weight of colloids Polymers, proteins and such macromolecules often form colloidal dispersions. The molecular weights of those molecules can be determined by ultracentrifugation. The larger molecules will be arranged at periphery and the lighter molecules near the center .